It is proposed to study in detail the mechanism of enzymatic dechlorination and the nature of the enzyme systems which catalyze these reactions. Several enzymatic dechlorination reactions have been reported in the literature which suggest reductive, oxidative, substitutive and hydrolytic mechanisms, although it is not clear presently what contribution each makes to the total dechlorination. The proposed studies will clarify this. The methods employed initially will be those developed in the laboratory of the Principal Investigator. These studies will be carried out in vitro in subcellular fractions of liver samples obtained from rats and humans. The studies eventually will concentrate on the components of the microsomal drug metabolizing system. Since recent studies have revealed that important differences exist between rat and human microsomal enzyme systems, the emphasis of the present study will be on understanding the human system although utilizing the rat system to develop the techniques. The studies will include the solubilization of microsomes, chromatographic separation of the microsomal components and attempts to reconstitute the dechlorinating enzyme system.